Children with fetal alcohol syndrome (FAS), suffer mental deficits that handicap them for life. Understanding how ethanol exerts its neuroteratogenic action at a cellular and molecular level may offer insights into the design of interventions to improve CNS functional outcomes for these individuals. In this regard, it is now clear that GABA/ARs are predominantly "excitatory/neurotrophic" transducers in developing brain and take on the better known, classical inhibitory role as the brain matures. Early GABA/ARs depolarize immature neurons, activating voltage-dependent Ca/2+ entry and stimulating neurogenesis, neuronal differentiation, migration as well as synaptogenesis. Currently, little is known about the impact of ethanol on the function or expression of "excitatory" GABA/ARs in the immature CNS. If ethanol distorts the normal developmental pattern of GABA/AR activity, this could contribute to neurological deficits in FAS. We have recently identified a delay in the postnatal evolution of GABA/ARs in rat medial septal/diagonal band (MS/DB) neurons one week after moderate "binge- like" postnatal ethanol exposure. Basic GABA/AR function recovers bu 4-5 weeks of life, but subtle longer-lasting changes in Zn/2+ inhibition remain. Impairment of early postnatal GABA/AR function in the MS/DB could distort appropriate synapse formation and contribute to attention deficits characteristic of individuals with FAS. This project will use well-established in vivo rodent models of FAS, in vitro primary neuronal culture systems, immunocytochemistry, stereology and in vitro electrophysiological recordings in individual neurons and brain slices to determine the impact of prenatal ethanol exposure on MS/DB functional development. These studies will test the hypothesis that: "Perinatal ethanol exposure inhibits excitatory GABA/ARs which interferes with normal patterns of neuronal development."